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Many phleboviruses (family Bunyaviridae) are emerging as medically important viruses. These viruses enter target cells by endocytosis and low pH-dependent membrane fusion in late endosomes. However, the necessary and sufficient factors for fusion have not been fully characterized. We have studied the minimal fusion requirements of a prototypic phlebovirus, Uukuniemi virus, in an in vitro virus-liposome assay. We show that efficient lipid mixing between viral and liposome membranes requires close to physiological temperatures and phospholipids with negatively charged headgroups, such as the late endosomal phospholipid bis(monoacylglycero)phosphate. We further demonstrate that bis(monoacylglycero)phosphate increases Uukuniemi virus fusion beyond the lipid mixing stage. By using electron cryotomography of viral particles in the presence or absence of liposomes, we observed that the conformation of phlebovirus glycoprotein capsomers changes from the native conformation toward a more elongated conformation at a fusion permissive pH. Our results suggest a rationale for phlebovirus entry in late endosomes.

Original publication

DOI

10.1074/jbc.M115.691113

Type

Journal article

Journal

J Biol Chem

Publication Date

18/03/2016

Volume

291

Pages

6412 - 6422

Keywords

bis(monoacylglycero)phosphate, bunyavirus, electron tomography, membrane, membrane fusion, phlebovirus, virus entry, virus structure, Animals, Cell Line, Cricetinae, Glycoproteins, Hydrogen-Ion Concentration, Liposomes, Lysophospholipids, Monoglycerides, Phlebovirus, Viral Proteins, Virus Internalization